1. Field of the Invention
This invention relates to novel synthetic N-formyl peptides in combination with antibiotics. More particularly, to certain N-formyl tri- and tetra-peptides useful as chemoattractants in combination with antibiotics such as silver sulfadiazine useful in inhibiting microorganisms.
2. Description of the Prior Art
Chemotaxis is the directed movement of cells along an increasing chemical gradient. Certain naturally occurring substances, such as C5a (a serum factor derived from complement) and compounds elaborated by bacteria, have been reported as being leukoattractants, i.e., having chemotactic activity for leukocytes. In addition to their chemotatic activity, such substances have been found to induce lysosomal enzyme secretion from the leukocytes, particularly in the presence of cytochalasin B. The size, complexity, and unknown structure of most of these leukoattractant substances, have precluded any definitive analysis of the structural of molecular basis of their chemotactic activity. It has been established that leukoattractants produced by E. coli, which are extremely potent and present in low concentrations in the cell culture medium, have as their active components small, heterogeneous peptides with blocked amino groups, but their low concentration levels have hampered further characterization.
Recent studies have produced substantial evidence to the effect that the naturally occurring leukoattractants elaborated by bacteria, together with the phenomenon of chemotaxis, play a major role in the first line of defense of the human body to bacterial infection. Thus, it is believed that the phagocytic or defense leukocytes, i.e., neutrophils, macrophages, basophils, and eosinophils, accumulate at sites of infection, in part, as a response to the leukoattractants secreted by the invading organisms. The leukoattractants then induce secretion from the phagocytes of the lysosomal enzymes which, in turn, attack and destroy the invading organisms. In addition, some of the phagocytes participate in the laying down of new connective tissue after the infection has been cured. Therefore, their appearance at the site of pathology is important in two respects, i.e., destroying the invading organisms and restoring the damaged tissue.
Silver sulfadiazine is the antibiotic commonly used to treat burns. However, silver sulfadiazine inhibits the migration of polymorphonuclear leukocytes and monocytes into the area of infection treated with the antibiotic. Therefore, a need exists for a method of stimulating the migration of polymorphonuclear leukocytes and monocytes into the area containing the antibiotic. Based upon the theory that leukoattractants in combination with antibiotics will promote migration of polymorphonuclear leukocytes and monocytes into an area otherwise inhibited by the antibiotic, experimental procedures were disclosed to produce a synthetic leukoattractant-antibiotic complex suitable for the purpose.
The following publications are herein incorporated by reference.
(1) Aswanikumar et al, Biochemical and Biophysical Research Communications 74:810, 1977;
(2) Altman et al, Journal of Immunology, 119:199, 1977;
(3) Warden et al, Annals Surgery, 181:363, 1975;
(4) Schiffmann et al, Proc. Nat. Sci. USA, 72:1059, 1975
(5) Altman et al, Journal of Surgical Research, 22:616, 1975;
(6) Fikrig et al, Ann. Surg. 186:746, 1977. Altman et al, Fed. Procedings 40:1103, 1981.